Pain is the main reason prompting patients to consult their physicians. In acute conditions,
pain has a very particular significance as a warning sign, enabling the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon the individual (even in the case of
acute pain) and its cost to society are now widely acknowledged. There can be no doubt about the physical component of
pain, but the psychological and social aspects should not be ignored, particularly in the case of
chronic pain. There is no single therapeutic approach to
pain and, more often than not, successful treatment comprises a combination of several. Pharmacological treatments are undeniably the most common approach. In clinical practice, recent advances have been based upon an improved understanding of 'old' substances such as
morphine and, at the same time, research continues in the hope of finding the 'ideal'
analgesic-effective in most situations but without adverse effects: this appears to be a somewhat utopian arm at present, considering the number of different causes of
pain. An improved understanding of the physiological mechanisms of
pain has led, within the field of clinical practice, to several methods of differentiating
pain. These depend on whether or not
pain responds to
morphine, or on the type of
pain:
pain due to an excess of nociception,
pain resulting from deafferentation (caused by damage to nerve pathways) in the central or peripheral nervous system and psychogenic (idiopathic)
pain. Likewise, there are several different ways of classifying
analgesic treatments: according to the intensity of
pain, as with use of the WHO ladder (which is based on the notion of steps) for the treatment of
cancer pain; according to the presumed physiopathological mechanism and, in particular, the response to
morphine, and according to the presumed central or peripheral mechanism of the drugs. In reality, peripherally acting drugs can also have a central mechanism of action, just as drugs known to have a central mechanism of action can also have peripheral activity. As a result, several therapeutic classes have been identified. Firstly
NSAIDs, which act by inhibiting the
enzymes that synthesise
prostaglandins,
cyclooxygenases (COX-1, COX-2), but which also act upon lipo-
oxygenases: Their efficacy is interesting, although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce. Specific inhibitors of COX-2 could well reduce the risk of adverse effects.
Opioids constitute the first-line treatment for
pain, particularly severe
pain. There are several classifications for these drugs. Firstly, weak
opioids (such as
codeine) and strong
opioids (such as
morphine) are differentiated. Secondly, a distinction is made between pure agonists (such as
morphine), partial agonists (such as
buprenorphine), agonist-antagonists (such as
nalbuphine) and antagonists (such as
naloxone). Finally, agents are distinguished on the basis of their chemical structure (synthetic, semi-synthetic or natural derivatives). These molecules act upon different
receptors (mu, delta, kappa, sigma) and, although peripheral mechanisms have been described, their activity occurs mainly at spinal and supraspinal levels. They provide a potent
analgesic effect but are also responsible for various adverse effects-
nausea,
vomiting, sedation,
constipation and
respiratory depression-which seriously limit their use. As long as the indication is appropriate, these drugs should not be withheld because of fear of dependence or abuse. It has been observed that other adjuvant therapeutic approaches, generally used to treat conditions other than
pain, provide
pain relief in certain situations. These include
corticosteroids, which are-widely used in rheumatology and oncology, and
antidepressants, which are frequently used to treat
chronic pain, especially that with a neuropathic component. Anti-epileptics are also used, particularly for excrutiating